Glucocorticoids are produced and secreted by the adrenal cortex. Glucocorticoids play a key role in metabolism and immune response and are typically involved in inflammation suppression. Cortisol is a glucocorticoid found in human plasma. Approximately 95% of the body's endogenous glucocorticoid supply is cortisol. Increased amounts of cortisol are released into the blood stream when the body is subjected to physiologic stresses such as illness or trauma.
The release of cortisol is regulated by a physiologic cascade which starts at the hypothalamus. The hypothalamus produces corticotropin-releasing factor (CRF). CRF stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). The adrenal glands are then stimulated by ACTH to secrete additional cortisol. Once the stressor-induced physiologic demands are met, the anterior pituitary is then stimulated to decrease production and release ACTH (Howser, R. L. (1995) "Corticosteroid Therapy" American Journal of Nursing: 44-49). Plasma cortisol levels typically vary between about 0.005 and 0.020 ng/ml normally.
It is known in the art and described for example, by Fox, S. I. (1984) "The Endocrine System, Steroid Hormones" Human Physiology, W. C. Brown Publishers: 564-595, that free cortisol in the blood stream is in equilibrium with cytoplasmic cortisol. However, in response to a physiologic stressor, such as trauma or disease, the cortisol equilibrium is upset and blood cortisol levels rise in response to the stressor.
Sophisticated wound diagnostics are not currently available to the wound care professional. Wound diagnosis is empirical and heavily relies on the experience and knowledge of the practitioner. Improperly diagnosed wounds such as diabetic ulcers, venous-stasis wounds and pressure sores frequently result in negative, sometimes devastating outcomes. In the past, visual wound assessments provided an indication of the approximate depth, width and discharge status of a wound. For example, venous-stasis wounds continuously discharge fluid and tend to be wide and shallow (e.g. one to two centimeters deep). Diabetic ulcers tend to be drier and deeper relative to venous-stasis ulcers. Both types of wounds are frequently found on the lower extremities of patients. Diabetic ulcers are generally found on the undersides of the feet while venous-stasis ulcers are generally found on the calves and shins. However, these wounds may also be found on the upper torso and arms. Visual wound assessments have proven to be inadequate for proper diagnosis, especially for chronic wounds. Many patients who show signs of improvement, e.g. wound-size shrinkage and discomfort reduction, subsequently develop opportunistic infection including gangrene often requiring limb amputations to save their lives.
In most cases, aggressive therapeutic intervention is not indicated after initial visual wound assessment because the practitioner is unaware of the nature and actual extent of the wound. For example, the application of a debriding agent (enzymes which destroy necrotic tissue) would be inappropriate for a chronic or exacerbated wound. Compression bandages applied to a misdiagnosed pressure sore would compromise the healing of an actual venous stasis ulcer. Fundamentally, the practitioner does not know whether a wound is likely to heal or not. Therefore, several months of trial and error therapies face a patient with a chronic, non-healing wound.
The present inventors have provided a rapid, accurate and non-invasive method to diagnose wound status in a manner which permits meaningful assessment of the wound for proper treatment and for assessing the advisability of tissue (e.g. skin) grafts. As uniquely determined by the present invention, chronic or exacerbated wounds can now be diagnosed by measuring free cortisol in wound fluid. In accordance with the present invention, it has been discovered that elevated levels of cortisol in wound fluid relative to normal plasma levels in healthy patients correlates with large, non-healing wounds. It has also been discovered herein that elevated levels of cortisol in wound fluid also correlate with inflammation and infection. Early detection of inflammation and infection in non-healing wounds permits the practitioner to begin antibiotic or anti-inflammatory regimens prior to or in conjunction with the employment advanced wound care products. Early detection of inflammation and infection in non-healing wounds also indicates the likelihood of tissue (e.g. skin) graft rejection.
Wound therapy assessment is also greatly enhanced by the present invention. In the past, the practitioner would treat a wound simply based on its outward appearance. For example, a veneous-stasis wound was conventionally treated with antibiotics, alginate dressings and/or tissue grafts. The process was hit or miss; if the prescribed treatments and/or tissue grafts were successful, then the patient was helped in the short term. But if the treatments were inappropriate, the patient could be faced with months of useless medication or additional tissue grafts, at significant cost. With the present invention, the practitioner can now quickly, more accurately and non-invasively determine the nature of a wound and prescribe an appropriate therapy for short-term remediation. The present invention provides the practitioner with crucial information about the nature and extent of the wound. Aggressive wound therapy can now be implemented or avoided depending on the wound fluid cortisol levels of a patient as determined by the present invention.